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Sebum Control
Nanoparticles and Light
Nitric oxide has been studied in wound healing,
cancer treatment and cardiovascular disease. And
it may soon become a valuable treatment tool for
dermatologists. Novan Therapeutics (novantherapeutics.com), a company developed to pursue a
variety of stabilized NO-based medical therapies,
is currently conducting Phase 2 clinical trials of
SB204, an NO-based topical for sebum reduction.
The company recently released a white paper,
"Topical Nitric Oxide as a First-in-Class, Local
Antiandrogen Therapy for the Treatment of Acne
and Male Pattern Baldness," by William Kelce,
PhD. "It shows multiple ways that NO could
either shut down androgen synthesis in the skin
or inhibit the conversion of testosterone to its active metabolites in the skin," says Nathan Stasko,
PhD, a chemist and co-founder of Novan.
The Innovation Factory—an
entrepreneurial incubator that
specializes in medical devices
and life sciences—has developed
Sebacia, a silica and gold-based
nanoparticle applied in a topical
cream that causes photothermal
damage to the sebaceous glands
when activated by wavelengths
commonly used in laser hair
removal devices.
The company partnered with
Rox Anderson at Massachusetts
General Hospital as a thought leader on the use of lasers in
dermatology, and Rice University which has a nanotechnology based on
a physics theory from the 1800s called the Mai Theory "where you can
basically engineer particles to preferentially absorb certain wavelengths
of light," says Todd Meyer, COO of Sebacia.
The microparticles include a silica sphere covered in a gold metallic
shell. "It's the ratio of diameter between the inner and outer shell that
allows you to tune the particle to a speciﬁc wavelength," he says.
They are delivered trans-follicularly into the sebaceous glands and
then irradiated with laser to selectively heat the gland. The particle was
designed to work with the 800nm wavelength, but is also effective with
other common laser hair removal wavelengths, including 755nm and
1064nm. "You design the particle to peak absorb speciﬁc wavelengths,
so there's a little bit of efﬁciency loss when you move off that peak,"
says Meyer.
The company has been conducting pilot studies outside of the
United States and has treated more than 100 patients, primarily in
facial acne. Their most recent study was a 48-patient, randomized,
active control, crossover study comparing the Sebacia treatment and
a 2% salicylic wash. Results were measured by lesion count. "At 12
weeks, we're looking at a mean reduction in inﬂammatory lesions of
35% in the treatment arm and 16% in the salicylic arm," says Meyer. "At
28 weeks, our mean in the treated population is -61%. The continued
improvement at 28 weeks is consistent with the proposed mechanism
of action in terms of the photothermal modiﬁcation of the gland."
In pre-clinical testing that mimicked clinical usage with multiple
exposures, the company reports a return to baseline levels of gold
within a month of treatment. "So basically zero gold," says Meyer. "As
far as we can tell, we think we're probably just expressing the gold
particle back out through the follicle."
He notes that there is no limitation on sun exposure following
treatment and patients' self-reported pain scores during treatment
were "about a three on a zero to 10 pain scale, so this is really a
procedure that patients can walk out of the ofﬁce and resume normal
daily life," he says.
Company-sponsored in vitro research conducted by Diane Thiboutot, MD, professor of
dermatology at Penn State Hershey College of
Medicine, showed that immortalized human
sebocytes treated with SB204 showed reduced
sebum production.
Additional research using the golden Syrian
hamster ﬂank organ model, showed that SB204
inhibited the growth of the hamster ﬂank organ
by more than 50% compared to vehicle control,
further suggesting anti-androgenic activity.
"The important thing is that it's local," says
Stasko. "The nitric oxide interacts with the surface of the skin, and your body never really sees
any of the systemic effects. It only acts right there
at the skin and it is transient."
The difﬁculty in developing NO-based therapies has been traditionally related to formulation.
"The biggest challenge is how do I get a sustained
release of a gas on the skin—that's really the
question, and our platform enables us to do this,"
says Stasko.
8 July/August 2013 | ACNE & ROSACEA
Photo courtesy of James Tunnell, PhD, University of Texas, Austin
Topical Nitric Oxide